39 results about "Liver toxicity" patented technology

The application discloses a compound Chinese herbal medicine fermentation preparation for preventing and treating hepatotoxicity of Penaeus vannamei and a preparation method thereof. Spore bacillus is used as a fermentation strain to perform aerobic fermentation on four traditional Chinese herbal medicine stem and leaf wastes, i.e. Astragalus stem and leaf, Rhubarb stem and leaf, Codonopsis stem and leaf and Coptis stem and leaf, so as to obtain a compound Chinese herbal medicine fermentation product with higher active substances. The compound Chinese herbal medicine fermentation preparation of the application can be added into the feed of Penaeus vannamei, so as to effectively prevent and treat hepatotoxicity of Penaeus vannamei.

The invention provides a tripterine sulfated metabolite and application thereof in preparation of a medicine for resisting rheumatoid arthritis, and belongs to the technical field of biological medicine. The tripterine sulfated metabolite is 10-sulfated tripterine which is formed by connecting a HSO3 <-> to the 10-position carbon of the tripterine. Compared with the tripterine, the 10-sulfonated tripterine has no obvious difference in anti-rheumatoid arthritis pharmacological activity, however, the hepatotoxicity in vivo and the cytotoxicity in vitro of the 10-sulfonated tripterine are obviously reduced. The tripterine sulfated metabolite is efficient and low in toxicity, and a wide application prospect is developed for treatment of rheumatoid arthritis.

Systems and methods consistent with the present invention generally relate to microorganospheres (MOSs), and methods and apparatuses for forming and using MOSs. More particularly, in some embodiments, systems and methods consistent with the invention relate to the methods and apparatuses for forming and using MOSs generated from hepatocytes. MOPSs that are generated from hepatocytes are suitable for testing liver toxicity and drug induced liver injury effects of various agents.

The application relates to an application of a SETDB1 activator in a medicine for treating organ injury and the medicine. The application of the SETDB1 activator in the medicine for treating organ injury is (R, R)-59. The application further provides a medicine for treating organ injury, and the medicine comprises the SETDB1 activator (R, R)-59. The application provides a new application of the SETDB1 activator (R, R)-59, and the SETDB1 activator (R, R)-59 can effectively relieve liver toxicity caused by hunger or other factors by regulating lipid toxicity and promoting lipid autophagy, the SETDB1 activator (R, R)-59 can inhibit inflammatory response and hepatocyte apoptosis caused by APAP overdose, promotes liver repair, and provides a new medicine for treating drug-induced liver injury.

The invention belongs to the technical field of traditional Chinese medicine preparations, and provides anti-cold granules and a preparation method thereof. The preparation method comprises the following steps: (1) preparing an extract: performing ultrasonic water extraction on honeysuckle flower powder to obtain a honeysuckle flower extract; performing ultrasonic extraction on the radix paeoniae rubra powder by adopting a composite solvent to obtain a radix paeoniae rubra water extract; adding a natural clarifying agent into the red paeony root water extract for clarifying, cooling, filtering, and concentrating under reduced pressure to obtain a red paeony root extract; carrying out ultrasonic water extraction on rhizoma dryopteris crassirhizomae, filtering, and carrying out vacuum concentration to obtain a rhizoma dryopteris crassirhizomae extract; (2) mixing the honeysuckle extract, the radix paeoniae rubra extract and the rhizoma dryopteris crassirhizomae extract, and performing vacuum concentration to obtain clear paste; and adding auxiliary materials into the clear paste to prepare the anti-cold granules. By adopting the preparation method, the dissolution of effective components in the anti-cold granules can be remarkably improved, and particularly the contents of paeoniflorin and chlorogenic acid are increased, so that the liver toxicity generated by the medicinal component phloroglucinol derivative of the rhizoma dryopteris crassirhizomae is balanced, and the effects of reducing toxicity and enhancing efficiency are achieved.

The present invention discloses the use of a short-term embolic agent in reducing drug accumulation in the liver, hepatic clearance and / or liver toxicity. The present invention provides the use of a short-term embolic agent in the manufacture of a medical composition for: (a) temporarily embolizing blood vessels supplying the liver; and (b) reducing the accumulation of a drug subsequently or concurrently administered intravenously in the liver. The strategy aims to minimize the exposure of a drug (such as LNP) to the liver by temporarily blocking the blood supply to the liver via the portal vein and / or arteries. The present invention significantly reduces the non-specific accumulation of a drug in the liver by temporarily blocking the portal vein, arterial and / or their branch blood flow, thereby greatly reducing the opportunity for the drug to enter the liver from a hemodynamic root.

The invention discloses a novel TNF-alpha targeted protein degradation agent for treating acute hepatic failure, the TNF-alpha targeted protein degradation agent can accurately remove excessive TNF-alpha to block a liver injury signal, and the defects that a traditional TNF-alpha inhibitor interferes tissue repair due to an overlong half-life period and an Fc fragment triggers an ADCC / CDC effect to cause drug-related hepatotoxicity are overcome. The pharmaceutical safety is improved while the treatment effectiveness is ensured, a better treatment choice is provided for acute hepatic failure and other TNF-alpha related diseases, and the pharmaceutical composition has a good clinical application prospect and an important conversion value.

The application relates to a method and system for establishing a prediction model of chemical liver toxicity, which comprises the following steps: (1) differentiating human embryonic stem cells or human induced pluripotent stem cells into hepatocyte-like cells and constructing a three-dimensional hepatocyte model; (2) taking miR-122, LDH and Cyto C in the three-dimensional hepatocyte as combined test indexes to judge liver toxicity of a liver toxicity mode compound; (3) classifying the liver toxicity mode compound into three categories through two canonical discriminant functions by a linear discriminant analysis modeling method; and (4) converting the canonical discriminant function into a Fishers discriminant function to obtain a liver toxicity prediction model. The application has the general characteristics of a conventional cell model for evaluating compounds, and can also evaluate the toxicity effect and health risk of the compounds in a high-throughput manner with relatively less manpower.

The invention belongs to the field of mRNA drugs, and particularly relates to an NQO1 responsive mRNA translation masking agent and application, a product and a method thereof. The molecular formula of the mRNA translation masking agent is C21H28N4O4, and the molecular formula of the mRNA translation masking agent is The mRNA translation masking agent can be covalently bound with mRNA through an acylation reaction to form steric hindrance inhibition translation, and efficiently recover the translation ability in an NQO1 high expression environment, so that the half-life period of mRNA in cells is prolonged, and the cumulative yield of target protein is also improved. The mRNA translation masking agent and the mRNA masking method thereof provided by the invention can be used for tumor targeted therapy, not only realizes specific removal of tumor cells, but also reduces hepatotoxicity. The technical scheme of the invention is helpful for developing safe, convenient and sensitive mRNA drugs for tumor targeted therapy.

Methods and uses are disclosed for treating a subject suffering from a disorder selected from a liver disorder, Cushing's syndrome, or Cushing's Disease, cancer, an infection, an inflammatory condition, a cardiovascular, endocrine, or kidney disease, and combinations thereof, or other disorder for which they may be administered a drug which may cause liver toxicity, without adverse effects on the liver. Such liver disorders include fatty liver diseases are effective for reducing high levels of liver enzymes with a favorable safety profile. The methods and uses comprise administering to the subject an effective amount of a selective nonsteroidal glucocorticoid receptor modulator such as relacorilant, including methods and uses in combination with another drug, without adverse effects on liver enzyme levels, or on liver function. In embodiments, the other drug may be a drug that may cause liver toxicity, such as drugs that inhibit CYP3A enzymes, e.g., itraconazole or ketoconazole.

The invention discloses a multi-modal hepatotoxicity prediction model determination method, and belongs to the technical field of big data processing. The method comprises the following steps: acquiring a drug-determination matrix of N rows and M columns, wherein the N rows comprise drug data of N drugs; the M column comprises measurement data of whether the medicine has a biological activity label or not under each target of the M targets; mapping K candidate determination data related to hepatotoxicity and F basic hepatotoxicity mechanism frameworks in the drug-determination matrix to obtain a biological fingerprint; determining heterogeneous data corresponding to each drug according to the chemical structure chart and the biological fingerprint of each drug in the N drugs; according to the drug data and the heterogeneous data of each drug, training the neural network prediction model until a preset training condition is met, and obtaining a multi-modal hepatotoxicity prediction model. Therefore, the cost of determining the hepatotoxicity of the compound can be effectively reduced without depending on experimental animals and manual operation, and the efficiency and accuracy of determining the hepatotoxicity of the compound are improved.

The invention belongs to the technical field of medicines, and particularly relates to itraconazole transdermal cream and a preparation method thereof. According to the itraconazole transdermal cream provided by the invention, the itraconazole and the clove essential oil are jointly applied by adopting an emulsification method, the limitation of single use of the itraconazole and the clove essential oil is broken through, the bioavailability of the itraconazole and the clove essential oil is improved, and the itraconazole transdermal cream acts on an infected part after being subjected to transdermal absorption through local administration, so that the itraconazole is absorbed into blood and reaches the skin of the whole body to play a role; the traditional Chinese medicine composition can achieve the same blood concentration and effect of oral administration, is convenient to use, reduces liver toxicity and gastrointestinal tract adverse reactions, and reduces the risk of adverse reactions and drug interaction at the same time.

The application discloses a vortioxetine impurity, a preparation method and application thereof, and adopts vortioxetine or a pharmaceutically acceptable salt form thereof as raw material, the raw material is easy to obtain and simple to operate, and the reaction condition is mild. The synthesized impurity is characterized by nuclear magnetic resonance, high-resolution mass spectrometry and X-ray single crystal diffraction, and liver toxicity research shows that the compound disclosed by the application has important significance for researching adverse reactions of vortioxetine. The control sample obtained by the method provided by the application can be used for qualitative and quantitative analysis of the vortioxetine impurity, so that the drug safety of vortioxetine is improved.

The application relates to the technical field of pharmaceutical preparations, and discloses an agomelatine inhalant as well as a preparation method and application thereof. The agomelatine inhalant provided by the application comprises agomelatine or a pharmaceutically acceptable salt thereof in a form capable of being inhaled or capable of being changed into a form capable of being inhaled after being excited. From the aspect of synergism, the inhalant can avoid first-pass metabolism by changing a drug administration route, significantly improve bioavailability, and realize rapid effect by directly entering blood from the lung; from the aspect of attenuation, the inhalant can greatly reduce a drug usage amount to achieve a same treatment effect as a tablet, significantly reduce occurrence of drug toxic and side reactions, and significantly reduce liver toxicity by avoiding liver metabolism.

The invention discloses a microfluidic device and a use method thereof, and relates to the technical field of microfluidics, the microfluidic device comprises a culture substrate unit, a first cell accommodating unit, a second cell accommodating unit and an interactive interface unit, the interactive interface unit is fixedly arranged between the first cell accommodating unit and the second cell accommodating unit, and the first cell accommodating unit is connected with the second cell accommodating unit. The interactive interface unit comprises a microporous structure allowing biomolecules to pass through, so that substance exchange and signal transmission between the first cell accommodating unit and the second cell accommodating unit are realized. According to the invention, an in-vitro model with high physiological correlation and accurate prediction is brought by accurately reproducing spatial tissues and dynamic microenvironments of organs, and a tissue and blood vessel interface is successfully simulated through combination of a separated co-culture structure and a dynamic fluid perfusion system, so that cells can be self-organized into a functionalized three-dimensional structure with polarity, and the functional three-dimensional structure with polarity is formed. Therefore, the sensitivity and the specificity which are far superior to those of a traditional model are realized in tests of drug hepatotoxicity and the like.

The application discloses application of a GPR120 agonist in preventing or treating intestinal-liver immunological injury induced by poultry acetochlor poisoning. According to the intestinal-liver toxicity of chicken acetochlor, the normal expression of G protein-coupled receptor 120 is mainly changed. Subsequently, programmed cell death occurs in the intestinal tract and the liver, and a large amount of inflammatory factor release is caused; the intestinal-liver axis immunological injury is improved by activating the G protein-coupled receptor 120 in vivo and in vitro, so as to rescue the chicken acetochlor poisoning reaction. The application provides a prevention and treatment basis for poultry acetochlor poisoning immunological injury diseases, provides medical data for developing poultry immunological activity drugs or supplements, and also provides more technical means for developing and utilizing environment-friendly, efficient, targeted and slow-release new veterinary drug preparations.

The invention relates to the technical field of biological medicines, in particular to a psoralen derivative and application thereof in preparation of a medicine for treating rheumatoid arthritis. According to the derivative, through an ester prodrug strategy, psoralen C8 / C5 hydroxyl and a non-steroidal anti-inflammatory drug are coupled to obtain a double-pharmacophore molecule. According to the invention, the problems of poor lipid solubility and high hepatotoxicity of psoralen are solved through an ester prodrug design strategy, a high-efficiency and low-toxicity novel drug candidate is provided for RA treatment, and the prepared psoralen derivative can effectively treat rheumatoid arthritis and complications thereof, and can significantly improve arthropathy caused by RA.

The invention discloses a medicine for treating drug-induced liver injury by taking a DDR1 gene or protein as a target spot, and belongs to the technical field of medicines. The drug-induced liver injury is caused by abnormal activation or accumulation of DDR1 protein, and the pathological characteristics of the drug-induced liver injury comprise nesting apoptosis of liver cells. The invention discloses that DDR1 is a key molecular target for inducing hepatotoxicity by the Platinib for the first time, and the Platinib can lead to obvious increase of DDR1 protein and phosphorylation level thereof at a treatment concentration, so that cell-ECM and cell-cell adhesion are damaged, and anoikis is activated. By inhibiting the expression of the DDR1 gene or inhibiting the activity and accumulation of the DDR1 protein, the hepatocyte apoptosis caused by the Platinib can be effectively reversed. The invention provides a new molecular target for intervening in the induced hepatotoxicity of the prilatinib, and provides a new strategy for clinically and safely treating RET fusion positive tumors by preparing a drug for preventing or treating drug-induced liver injury by utilizing a substance for inhibiting the targeted DDR1.

The present application relates to a kind of in vitro 3D liver model and enterohepatic co-culture model and its establishment method and application, belong to the technical field of drug evaluation.The method includes the following steps: cell culture: HepaRG cell and human hepatic stellate cell are respectively carried out cell culture, standby;Cell induction: the above-mentioned HepaRG cell is seeded in culture flask and is carried out cell culture, after HepaRG cell adherent growth reaches predetermined quantity, it is replaced with induction medium and is carried out induction culture, and the induced HepaRG cell is obtained, standby;Model construction: the induced HepaRG cell and human hepatic stellate cell are made into mixed cell suspension, seed on predetermined carrier, culture, obtain the microtissue with the three-dimensional structure of liver nodule, i.e. 3D liver model.The model has the three-dimensional structure of liver nodule microtissue of liver, can well simulate the actual physiological condition of in-vivo liver, to accurately predict the liver toxicity of drug.

The invention provides an application of selenium-rich probiotics in preparation of a preparation for treating fluoxetine-induced liver injury, and relates to the technical field of biological medicine, the application is characterized in that Se-BL is obtained by reducing sodium selenite through ascorbic acid and modifying the surface of bifidobacterium longum, and nano-scale selenium dots are formed. The preparation plays a role through dual mechanisms: active oxygen (ROS) is directly removed, an Nrf2 pathway is activated, and the liver oxidation resistance (GSH, SOD) is improved; the traditional Chinese medicine composition is capable of inhibiting NF-kappa B inflammation signal channels, reducing proinflammatory factors (TNF-alpha and IL-6) and synchronously regulating intestinal flora so as to enhance the intestinal barrier function. Experiments prove that the traditional Chinese medicine composition can remarkably reduce the level of serum transaminase (ALT / AST / ALP) and relieve liver tissue necrosis and lipid peroxidation damage (MDA), the dosage form of the traditional Chinese medicine composition is an oral preparation, and each dose of the traditional Chinese medicine composition contains 1 * 10 <-1 > * 10 <-1 > CFU of Se-BL viable bacteria. The selenium-modified probiotics are used for antagonizing hepatotoxicity of mental drugs for the first time, and an innovative therapy is provided for fluoxetine-induced drug-induced liver injury (DILI) and acute hepatic failure (ALF).

The disclosure relates to formulations and methods for the in chemico testing of toxins based on a discovery that measuring a reduction in enzyme activity can be used to predict in vivo toxicity, including for example, a skin corrosion, skin irritation, eye corrosion, eye irritation, lung toxicity, liver toxicity, nervous system toxicity, developmental toxicity, acute toxicity etc. Disclosed methods are rapid, easy to perform and shelf-stable approaches for identification of toxic chemicals and materials.

The present invention relates to a formulation in particular an oral formulation for the prophylaxis and treatment of TG2-related disorders like fibrosis in particular diabetic nephropathy and / or diabetic associated non-alcoholic steatohepatitis (NASH) and / or non-alcoholic steatohepatitis, and its use in the prophylaxis and / or treatment of fibrosis in particular nephropathy, NASH, idiopathic pulmonary fibrosis, and cystic fibrosis. Further, the present application relates also to the use of (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate as hepatoprotectant, i.e. as hepatoprotective agent. In addition the present invention relates to a pharmaceutical composition comprising (S,E)-methyl-7-(1-(2-(2-ethylbutylamino)-2-oxoethyl)-2-oxo-1,2-dihydro-pyridin-3-ylamino)-6-(1-methyl-1H-imidazole-5-carboxamido)-7-oxohept-2-enoate for use as hepatoprotective agent and for use in the protection of the liver against liver toxicity, the improvement of liver function, and / or in the prophylaxis or treatment of a liver disease or liver disorder.

This invention belongs to the field of natural product extraction and biomedicine technology, and discloses a carrageenan polysaccharide ATSP-1 derived from Taxus chinensis and its applications. This polysaccharide, obtained through hot water extraction and purification, has a triple helix conformation, is mainly composed of galactose, has a weight-average molecular weight of 725.95 kDa, and its backbone contains specific glycosidic bonds and differentiated sulfation patterns. ATSP-1 can upregulate the expression of MHC-I / II molecules in colonic tissue through the antigen presentation signaling pathway, thereby activating CD4+. + / CD8 + It induces specific immune responses mediated by T cells; simultaneously activates the p53 apoptosis pathway, induces tumor cell apoptosis, achieves a tumor inhibition rate of 43.14%, and has no significant liver toxicity. It can be used to prepare immune-related anti-tumor products and provides natural active polysaccharide resources.

The invention belongs to the technical field of biological medicine, and particularly relates to an extrahepatic targeting lipid nanoparticle composition and application thereof. The lipid nanoparticle composition is prepared from the following raw materials: SM1012, DSPC (Distearoyl Pyrrolidone), beta-sitosterol and DMG-PEG (Dimethyl Glycol-Polyethylene Glycol) The DSPC accounts for 20%-30% of the lipid nanoparticle composition in percentage by mole. The lipid nanoparticles can significantly change the in-vivo distribution behavior in different injection modes. Different from the characteristic that a large number of traditional lipid nanoparticles are enriched in the liver after being injected in different modes such as intramuscular injection, the lipid nanoparticles can effectively reduce targeted aggregation towards the liver after being injected in the same way, so that high-concentration retention and enrichment in a local injection area are realized, and the lipid nanoparticles have the advantages of high bioavailability and high bioavailability. The bioavailability of the medicine at a target part can be improved, the whole body exposure and the potential hepatotoxicity are reduced, and a better delivery strategy is provided for local precise administration.

The present invention relates to a novel coronavirus recombinant spike protein, a polynucleotide encoding the same, a vector comprising the polynucleotide, and a vaccine for preventing or treating coronavirus infection, comprising the vector. The coronavirus recombinant spike protein of the present invention is stable and thereby not easily decomposed in cells, and effectively activates immune cells thereby resulting in a high antibody production amount and T cell reactivity. It was confirmed that the vector of the present invention exhibits a high antigen expression level and thereby has a high antibody production amount and T cell reactivity, has a long antibody production period and expression period, and does not show liver toxicity. Accordingly, the vector of the present invention can be helpfully used as a vaccine for preventing or treating coronavirus infection.

The invention discloses an in-vitro hepatotoxic drug screening method based on a high-throughput plug-in chip, and belongs to the technical field of plug-in chip drug toxicity screening. According to the method, a high-throughput plug-in chip is composed of a pore plate layer, a channel layer and a plug-in; every three holes form a chip unit, separation and material exchange between the pore plate layer and the channel layer are carried out through the porous membrane on the plug-in, and gravity flow is provided through the swing table; the chip hole pitch accords with the specification of a commercial pore plate, and is compatible with various analytical instruments. Through liver chip model construction, drug incubation testing and data processing analysis, efficient hepatotoxicity drug screening is realized. According to the invention, the human adult stem cell-derived liver organs are used for establishing the chip model, and the physiological correlation of the cells is strong; compared with a mouse model, human physiological liver parenchyma characteristics can be better simulated; the operation is simple and the consumed time is short. The method realizes high-efficiency and high-reproducibility drug screening, and plays a great role in the fields of basic research, transformation application and the like of preclinical tests of drugs.

The invention belongs to the field of biological medicines, and provides an application of acetoacetic acid and derivatives thereof in preparation of medicines for treating or relieving hepatotoxicity caused by antituberculosis medicines. The hepatocytes formed by differentiation of human induced pluripotent stem cells are verified, and hydrazine is a metabolite with the strongest toxicity, so that the content of acetoacetic acid in the metabolite in the cells is reduced. Acetoacetic acid is one of main ketone metabolites in the ketone metabolism process, and cells can convert acetoacetic acid into acetoacetyl coenzyme A through succinyl coenzyme A: 3-oxo acid coenzyme A transferase. According to the invention, the OXCT1 gene in the human induced pluripotent stem cell is knocked out through CRISPR-cas9 and the human induced pluripotent stem cell is differentiated into the hepatocyte, so that the knockout of the OXCT1 gene increases the content of acetoacetic acid and reduces hepatic differentiation cell death caused by hydrazine.

The present application relates to a kind of testosterone microcrystal, freeze-dried powder injection, suspension and its preparation method.The particle size range of testosterone microcrystal meets: D90≤20 μm.Testosterone microcrystal freeze-dried powder injection includes testosterone microcrystal, suspending agent and freeze-drying protective agent;The mass ratio of the suspending agent and the mass of the testosterone microcrystal meets (0.3-2):1.The particle size range of the testosterone microcrystal meets: D90≤20 μm.Testosterone microcrystal suspension includes water, testosterone microcrystal, suspending agent and freeze-drying protective agent;The concentration of the suspending agent is 0.3%-2%.The preparation of testosterone microcrystal prepared in the present application is short-acting preparation, has the advantages of small liver toxicity, dose accuracy and easy to use.

The invention belongs to the technical field of natural product extraction and biological medicine, and discloses carrageenan polysaccharide ATSP-1 derived from sea asparagi and application of the carrageenan polysaccharide ATSP-1. The polysaccharide is obtained through hot water extraction, separation and purification, has triple helix conformation, is mainly composed of galactose and has the weight-average molecular weight of 725.95 kDa, and a framework contains specific glucosidic bond connection and differential sulfation modes. The ATSP-1 can up-regulate the expression of MHC-I / II molecules in colon tissues through an antigen presentation signal channel, so as to activate CD4 < + > / CD8 < + > T cell mediated specific immune response; meanwhile, a p53 apoptosis pathway is activated, tumor cell apoptosis is induced, the tumor inhibition rate reaches 43.14%, no obvious hepatotoxicity exists, the polysaccharide can be used for preparing immune-related anti-tumor products, and a natural active polysaccharide resource is provided.